Nitin G. Rathod and Manohar V. Lokhande
The process related unknown impurity associated with the synthesis of Amodiaquine hydrochloride bulk drug was detected by high performance liquid chromatography (HPLC), was subjected to ion trap mass spectroscopy for preliminary determination of mass for identification. It was difficult to elucidate the structure with only iontrap ms and ms/ms since it is having a unit mass resolution it became important to isolate the impurity using preparative chromatography for further study. The preparatively isolated impurity was subjected to a high resolution accurate liquid chromatography mass spectroscopy (HR/AM-LCMS) for determination of molecular formula which gave a highly confident and accurate data for structure elucidation. The postulated structure was unambiguously confirmed by 1H NMR and 13C NMR was proposed to be 1, 1-bis-(7-chloro-4- hydroxy-3-quinolyl}-ethane (AMQ Dimer). This AMQ Dimer impurity was not been previously reported in any of the analytical literature pertaining to Amodiaquine hydrochloride. A rapid Acquity H-class gradient method with runtime of 15.0min was developed for Quantitation a C18 Hypersil gold column (100 mm x 2.1 mm i.d. 1.9 μm) was used for chromatographic separation and validated for parameters such as precision, accuracy, linearity and range, robustness. The limit of detection (LOD) established for AMQ Dimer impurity was found to be 0.0197ppm i.e. 0.012% and limit of quantification (LOQ) was found to be 0.0598ppm respectively.
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